The present invention relates to novel amidinonaphthyl furancarboxylate derivatives and acid addition salts thereof, and pharmaceutical compositions containing them (either alone or in combination with at least one pharmaceutically acceptable carrier). The present invention also concerns methods of treating nephritis, methods of treating auto-immune diseases, methods of treating arthritis, and a method of at least partially inhibiting the in vitro activity of trypsin, plasmin, thrombin, kallikrein and/or complement in biological samples.
Various autoimmune diseases are known, including, for example, systemic lupus erythematosus, articular rheumatism, scleroderma, etc. Pharmaceuticals generally known at present for treating these diseases are steroidal agents. Steroidal agents are very difficult to use properly; for example, erroneous use of steroidal agents causes various side effects due to the lowering of immunological functions or the atrophy of the adrenal gland, and sometimes ultimately causes death.
It is generally said that nephritis and autoimmune diseases are closely related with proteases and complement.
Amidinonaphthyl furancarboxylate derivatives are known to have activities of inhibiting enzymes such as trypsin, plasmin, kallikrein, thrombin, etc., and of inhibiting complement. It has been suggested that these enzyme inhibitors are useful as agents for the treatment of pancreatitis, agents for the treatment of hemorrhagic diseases, agents for the treatment of thrombosis or agents for the treatment of nephritis (Japanese Patent Kokai (Laid-open) Nos. 59-139357 and 61-22075).
However, though these compounds all show strong antienzyme activities, they are not yet satisfactory in their effectiveness and safety.